This study aimed to assess and compare the efficacy of LLLT and Calcium Hydroxide (CH) as intracanal medication in alleviating post-operative pain, percussion sensitivity, and in reducing the levels of IL-8 and substance P in periapical exudate one week after root canal instrumentation in patients with symptomatic apical periodontitis.<h4>Methodology</h4>This comparative, parallel-design randomized clinical trial evaluated the effectiveness of low-level laser therapy (LLLT) versus Calcium Hydroxide in managing post-operative pain in 48 patients with symptomatic apical periodontitis. This evidence concerns the gene TAC1 and periapical periodontitis.